Mutations in a new cytochrome P450 gene in lamellar ichthyosis type 3
| Autor: | Judith Fischer, Bakar Bouadjar, Gianluca Tadini, Véronique Ferrand, André Mégarbané, Jean François Prud'homme, Mark Lathrop, Caroline Lefèvre |
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| Rok vydání: | 2006 |
| Předmět: |
Genetic Markers
Male Enzyme complex Genetic Linkage Amino Acid Motifs DNA Mutational Analysis Molecular Sequence Data Mutation Missense Loss of Heterozygosity ALOX12B Protein Sorting Signals Linkage Disequilibrium ALOXE3 Cell Line Consanguinity CYP4F22 Cytochrome P-450 Enzyme System Congenital ichthyosis Genetics medicine Humans Tissue Distribution Amino Acid Sequence Lebanon ABCA12 Molecular Biology Genetics (clinical) biology Reverse Transcriptase Polymerase Chain Reaction Ichthyosis Chromosome Mapping General Medicine Lamellar ichthyosis medicine.disease Pedigree Molecular Weight Haplotypes Italy Algeria Case-Control Studies Mutation biology.protein Female France Chromosomes Human Pair 19 Gene Deletion Ichthyosis Lamellar Microsatellite Repeats |
| Zdroj: | Human Molecular Genetics. 15:767-776 |
| ISSN: | 1460-2083 0964-6906 |
| Popis: | We report the identification of mutations in a non-syndromic autosomal recessive congenital ichthyosis (ARCI) in a new gene mapping within a previously identified locus on chromosome 19p12-q12, which has been defined as LI3 in the OMIM database (MIM 604777). The phenotype usually presents as lamellar ichthyosis and hyperlinearity of palms and soles. Seven homozygous mutations including five missense mutations and two deletions were identified in a new gene, FLJ39501, on chromosome 19p12 in 21 patients from 12 consanguineous families from Algeria, France, Italy and Lebanon. FLJ39501 encodes a protein which was found to be a cytochrome P450, family 4, subfamily F, polypeptide 2 homolog of the leukotriene B4-omega-hydroxylase (CYP4F2) and could catalyze the 20-hydroxylation of trioxilin A3 from the 12(R)-lipoxygenase pathway. Further oxidation of this substrate by the fatty alcohol:nicotinamide-adenine dinucleotide oxidoreductase (FAO) enzyme complex, in which one component, ALDH3A2, is known to be mutated in Sjögren-Larsson syndrome (characterized by ichthyosis and spastic paraplegia), would lead to 20-carboxy-(R)-trioxilin A3. This compound could be involved in skin hydration and would be the essential missing product in most forms of ARCI. Its chiral homolog, 20-carboxy-(S)-trioxilin A3, could be implicated in spastic paraplegia and in the maintenance of neuronal integrity. |
| Databáze: | OpenAIRE |
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